Although Pap smears are properly credited for the marked reduction of cervical cancer mortality in the USA over the past 40 years, a single Pap Smear often fails to detect co-existing cervical neoplasia. This low sensitivity of Pap smear for detection of disease may be especially harmful for older women who are at an increased risk of cancer and for women who are not screened regularly. The aim of the project is to evaluate if diagnosis of HPV DNA in the genital tract is a useful adjunct to Pap smears in a cervical cancer screening program in economically disadvantaged older women. About thirty-five hundred women 40-70 years old in East Baltimore communities will be recruited through community organization, church fairs, door-to-door or leafletting and advertisement in newspapers. They will undergo screening for cervical cancer and cervical cancer precursor lesions by three tests: Pap Smear, HPV DNA detection by PCR and cervicography. Women found to be abnormal in any of the screens will be referred to colposcopy. Cervical biopsy will be obtained if abnormal areas are seen by colposcopy. With biopsy-proven disease as the reference, it is anticipated that HPV DNA detection and cervicography will increase the sensitivity of disease detection, from 0.7 for cytology alone to 0.95 for the three tests. Data will be examined to determined how the specificity of disease detection can also be maintained at a high level. Steps which might conceivably be useful in this regard are: (i) limiting analysis to cancer-associated HPVs; (ii) taking into account the quantity of viral DNA in the sample; and (iii) confining analysis to post-menopausal women, sexually inactive women and women with a smoking history. In a prospective component of the study, normal women (negative in all screens) and "at-risk" women (women with abnormal screens but without biopsy-proven disease) will be monitored annually for two years to compare cervical neoplasia incidence rates in the two groups. The data will be analyzed to identify factors which are predictive of cervical neoplasia. The results of this project will help determine if HPV DNA detection, as an adjunct to Pap smear examination, has any role in detection of cervical neoplasia in older women.